Etretinate A Review of its Pharmacological Properties and Therapeutic Efficacy in Psoriasis and Other Skin Disorders

Abstract

Etretinate (Ro 10-9359) is a new aromatic retinoic acid derivative for the treatment of severe psoriasis and other dyskeratoses. The pharmacological profile of etretinate suggests that it acts by normalizing pathological changes in epidermal and dermal skin, particularly inhibiting hyperkeratinization and cell differentiation, although its specific mode of action in different disorders remains to be elucidated. Etretinate is rapidly and presystemically metabolised to an active metabolite which appears in plasma at about the same time as parent drug. A 'deep' storage compartment with a very extended elimination half-life gives rise to detectable plasma levels of drug for at least 3 to 4 months after discontinuation of long term therapy. Studies suggest that etretinate at an initial dose of 1 mg/kg/day, reducible during maintenance therapy, is an effective alternative to PUVA and other conventional therapy in severe psoriasis. Its greatest immediate value is in the control of eruptive and treatment-resistant psoriasis, and in its potential for use in combination with other therapy to improve the response. In Darier's disease it appears to be the treatment of choice, and preliminary studies also suggest its usefulness in ichthyosis, and most other dyskeratoses and possibly in basal cell carcinoma. Side effects affecting the mucocutaneous system occur in nearly all patients, but rarely lead to drug withdrawal. When withdrawal does become necessary, the primary reason is usually hair loss. A few paradoxical observations of raised and lowered liver enzyme levels have been reported, and also a few cases of suspected liver damage. Etretinate is strictly contraindicated in women of child-bearing potential due to its severe teratogenic properties.

Retinoic Acid Attenuates Rheumatoid Inflammation in Mice

“…It has antitumor and diverse immunomodulatory actions (8), and it has been used for the treatment of acute promyelocytic leukemia (9) and inflammatory skin diseases like acne (10) and psoriasis (11). Retinoic acid also has been demonstrated to regulate reciprocal differentiation between regulatory T cells and Th17 cells.…”

Ursodeoxycholic acid as adjunctive therapy for problematic type 1 autoimmune hepatitis: A randomized placebo-controlled treatment trial

“…1,2 These latter patients require repeated or indefinite treatment, and side effects associated with long-term management may be limiting. [3][4][5][6] Ursodeoxycholic acid is the 7␤-hydroxy epimer of chenodeoxycholic acid, 7 and its administration has been associated with improvements in hepatic dysfunction. [8][9][10] It is now a standard therapy for primary biliary cirrhosis (PBC), 11 and preliminary reports have suggested efficacy in chronic hepatitis, 12 including AIH.…”

Effect of Retinoids on Proliferation of Human Embryonic Palatal Mesenchymal Cells in Culture

“…?_), has been utilized for the treatment of dermatologic disorders since 1982 (8). Retinoic acids have been reported to produce multiple abnormalities including limb deformities, heart de fects, and facial malformations in mammals and have similar teratogenic effects in humans (9)(10)(11)(12)(13).…”